Effectiveness of screening endoscopy for esophageal squamous cell carcinoma in Japanese males.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) has a poor prognosis; therefore, early detection is essential. In Japan, more than 90% of esophageal cancers are ESCC. Endoscopy is effective to detect ESCC in the early stage, but there is a limited number of reports examining its efficacy and effectiveness. OBJECTIVE: This study aimed to evaluate the efficacy of screening endoscopy for detecting ESCC. METHODS: This retrospective study analyzed the prevalence of ESCC, annual transition of prevalence, and the stage of each ESCC among 128,520 medical check-up patients who underwent esophagogastroduodenoscopy from April 2015 to March 2020 at Yamanashi Koseiren Health Care Center. Furthermore, a case-control study utilized the multivariate logistic regression analysis was performed to assess the risk factor of ESCC. RESULTS: Among a total of 128,520 subjects, 42 ESCC patients were detected, with 95.2% being diagnosed at early stages. Annual prevalence in males was 0.015% (2/13,122) in 2015, 0.044% (6/13,562) in 2016, 0.044% (6/13,676) in 2017, 0.074% (10/13,488) in 2018%, and 0.11% (16/14,386) in 2019. ESCC prevalence has been increasing each year. A significant increase was observed between 2015 and 2018 (p = 0.039). ESCC prevalence was 0.102% (25/24,272) when focusing on males aged over 50 years with a history of smoking and drinking. Regarding the case-control study, the multivariate logistic regression analysis revealed smoking (p = 0.044), mean corpuscular volume (MCV) (p = 0.0018), and severe gastric atrophy (p = 0.048) as positively correlated with ESCC. CONCLUSION: In conclusion, ESCC has been increasing in our center from 2015 to 2019, and the prevalence has been approaching that of gastric cancer in 2019 in male subjects. ESCC can be detected efficiently by targeting males with high MCV who have a history of drinking and smoking.

Reduction in asthma exacerbation rate after mepolizumab treatment initiation in patients with severe asthma: A real-world database study in Japan.

OBJECTIVE: To investigate the changes in asthma exacerbation, as well as in oral corticosteroid (OCS) use, exacerbation-related healthcare resource utilization (HRU), and healthcare costs before and after mepolizumab treatment initiation in patients with severe asthma who started treatment with mepolizumab in a real-world clinical setting in Japan. METHODS: A retrospective, observational, self-controlled study was conducted in Japan using a hospital-based administrative claims database. Patients who were diagnosed with asthma and who were new users of mepolizumab were included in the study. The primary outcome was the incidence rate of any asthma exacerbation/patient-year during the 12-month period before (baseline period) and after (follow-up period) the first mepolizumab prescription. Secondary outcome measures included the proportion of patients with ≥1 any asthma exacerbation, patients with exacerbation requiring hospitalization, the incidence rate of exacerbations requiring hospitalization/patient-year, the median daily OCS dose (OCS sparing effect), exacerbation-related HRU (hospitalization length, the proportion of patients with emergency visits, and the number of emergency/outpatient visits), and associated costs. RESULTS: Of the 377 patients included, 56.2% were ≥65 years of age. Following the first mepolizumab prescription, incidence rates for any asthma exacerbation were reduced by 40.6% (4.00/patient-year to 2.38/patient-year; the incidence rate ratio [95% confidence interval]: 0.60 [0.53-0.67]; p < 0.0001) from the baseline to follow-up periods. The incidence rate of exacerbations requiring hospitalization was reduced by 55.8% (0.37/patient-year to 0.16/patient-year) from the baseline to follow-up periods. The proportion of patients experiencing any exacerbation decreased from 84.4% to 57.8% and those requiring hospitalization decreased from 23.9% to 10.3% both from the baseline to follow-up periods. The median daily OCS dose decreased by 44.6% (median [interquartile range]: 6.7 [4.7-9.9] mg/day to 3.3 [0.9-5.6] mg/day) from the last baseline quarter to the 4th quarter of the follow-up period. All exacerbation-related HRUs decreased from the baseline to follow-up periods. Inpatient cost reduced by >50% (123,279 Japanese Yen [JPY]/patient-year vs. 57,283 JPY/patient-year), reducing the total cost by 80,716 JPY from the baseline to follow-up periods. CONCLUSION: Mepolizumab was effective in treating patients with severe asthma by reducing the incidence rates of exacerbations and exacerbation requiring hospitalization, OCS dose, exacerbation-related HRU, and cost in routine clinical practice in Japan.

The IMPACT Study - Single Inhaler Triple Therapy (FF/UMEC/VI) Versus FF/VI And UMEC/VI In Patients With COPD: Efficacy And Safety In A Japanese Population.

Purpose: The Informing the Pathway of COPD Treatment (IMPACT) study demonstrated that single-inhaler triple therapy fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) reduces moderate/severe exacerbation rates and improves lung function and health status versus FF/VI or UMEC/VI dual therapy in patients with symptomatic COPD and a history of exacerbations. This analysis evaluated the efficacy and safety of FF/UMEC/VI in patients enrolled in Japan. Patients and methods: IMPACT was a 52-week, randomized, double-blind, multicenter study comparing FF/UMEC/VI 100/62.5/25 µg with FF/VI 100/25 µg or UMEC/VI 62.5/25 µg in patients ≥40 years with symptomatic COPD and ≥1 moderate/severe exacerbation in the previous year. Endpoints included annual rate of on-treatment moderate/severe exacerbations (primary endpoint), time-to-first on-treatment moderate/severe exacerbation and change from baseline at Week 52 in trough FEV1, post-bronchodilator FEV1, St. George's Respiratory Questionnaire, and COPD Assessment Test score. Safety was also assessed. Results: The Japan subgroup accounted for only 4% (378/10,355) of the overall IMPACT intent-to-treat (ITT) population. In the Japan subgroup, FF/UMEC/VI reduced the annual rate of on-treatment moderate/severe exacerbations by 15% (95% CI: -20, 40) versus FF/VI (compared with 15% [10, 20] in the ITT) and 36% (95% CI: 6, 57) versus UMEC/VI (compared with 25% [19, 30] in the ITT). FF/UMEC/VI reduced moderate/severe exacerbation risk (time-to-first), improved lung function and health status at Week 52 versus both dual therapies. These results were in the same direction and of a generally similar magnitude to those seen in the overall ITT population. No new safety signals were identified in the Japan subgroup compared with the ITT population. Pneumonia incidence was higher with FF/UMEC/VI and FF/VI versus UMEC/VI. Conclusion: These results highlight the favorable benefit-risk profile of FF/UMEC/VI single-inhaler triple therapy compared with FF/VI or UMEC/VI dual therapy in patients in Japan with symptomatic COPD and ≥1 exacerbation in the prior year.

Pseudoaneurysm caused by a self-expandable metal stent: a report of three cases.

We present three cases of pseudoaneurysm caused by self-expandable metal stents that formed arteriobiliary fistulas and caused hemobilia. Diagnoses were made on the basis of dynamic computed tomography or angiography. One patient died because of bleeding and cholangitis, whereas the others were successfully treated by transarterial embolization.

1α,25-Dihydroxyvitamin D3 enhances cerebral clearance of human amyloid-ß peptide(1-40) from mouse brain across the blood-brain barrier.

BACKGROUND: Cerebrovascular dysfunction has been considered to cause impairment of cerebral amyloid-ß peptide (Aß) clearance across the blood-brain barrier (BBB). Further, low levels of vitamin D are associated with increased risk of Alzheimer's disease, as well as vascular dysfunction. The purpose of the present study was to investigate the effect of 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3), an active form of vitamin D, on cerebral Aß clearance from mouse brain. METHODS: The elimination of [125I]hAß(1-40) from mouse brain was examined by using the Brain Efflux Index method to determine the remaining amount of [125I]hAß(1-40) radioactivity after injection into the cerebral cortex. [125I]hAß(1-40) internalization was analyzed using conditionally immortalized mouse brain capillary endothelial cells (TM-BBB4). RESULTS: Twenty-four hours after intraperitoneal injection of 1,25(OH)2D3 (1 µg/mouse), [125I]hAß(1-40) elimination from mouse brain was increased 1.3-fold, and the level of endogenous Aß(1-40) in mouse brain was reduced. These effects were observed at 24 h after i.p. injection of 1,25(OH)2D3, while no significant effect was observed at 48 or 72 h. Vitamin D receptor (VDR) mRNA was detected in mouse brain capillaries, suggesting that 1,25(OH)2D3 has a VDR-mediated genomic action. Furthermore, forskolin, which activates mitogen-activated protein kinase kinase (MEK), enhanced [125I]hAß(1-40) elimination from mouse brain. Forskolin also enhanced [125I]hAß(1-40) internalization in TM-BBB4 cells, and this enhancement was inhibited by a MEK inhibitor, suggesting involvement of non-genomic action. CONCLUSIONS: The active form of vitamin D, 1,25(OH)2D3, appears to enhance brain-to-blood Aß(1-40) efflux transport at the BBB through both genomic and non-genomic actions. Compounds activating these pathways may be candidate agents for modulating Aß(1-40) elimination at the BBB.

Cerebral clearance of human amyloid-beta peptide (1-40) across the blood-brain barrier is reduced by self-aggregation and formation of low-density lipoprotein receptor-related protein-1 ligand complexes.

Soluble amyloid-beta peptide (Abeta) exists in the form of monomers and oligomers, and as complexes with Abeta-binding molecules, such as low-density lipoprotein receptor-related protein-1 (LRP-1) ligands. The present study investigated the effect of self-aggregation and LRP-1 ligands on the elimination of human Abeta(1-40) [hAbeta(1-40)] from the rat brain across the blood-brain barrier. Incubation of [(125)I]hAbeta(1-40) monomer resulted in time-dependent and temperature-dependent dimer formation, and the apparent elimination rate of [(125)I]hAbeta(1-40) dimer was significantly decreased by 92.7% compared with that of [(125)I]hAbeta(1-40) monomer. Pre-incubation with LRP-1 ligands, such as activated alpha2-macroglobulin (alpha2M), apolipoprotein E2 (apoE2), apoE3, apoE4, and lactoferrin, reduced the elimination of [(125)I]hAbeta(1-40). By contrast, pre-administration of the same concentration of these molecules in the rat brain did not significantly inhibit [(125)I]hAbeta(1-40) monomer elimination. Purified [(125)I]hAbeta(1-40)/activated alpha2M complex and [(125)I]activated alpha2M were not significantly eliminated from the rat brain up to 60 min. MEF-1 cells, which have LRP-1-mediated endocytosis, exhibited uptake of [(125)I]activated alpha2M, and enhancement of [(125)I]hAbeta(1-40) uptake upon pre-incubation with apoE, suggesting that [(125)I]activated alpha2M and [(125)I]hAbeta(1-40)/apoE complex function as LRP-1 ligands. These findings indicate that dimerization and LRP-1-ligand complex formation prevent the elimination of hAbeta(1-40) from the brain across the blood-brain barrier.